The Keystone Symposium entitled "Gene Therapy and Molecular Medicine" is designed to bring together basic science and clinical investigators in a unified effort to expedite the development of somatic gene therapy as a new treatment modality for a variety of human diseases. Gene Therapy as a biomedical discipline was originally conceived as an ultimate approach to provide permanent cures for genetic disorders. Early investigations focused on the "ex vivo paradigm" for gene therapy in which cells or tissues are obtained from the patients, cultured in vitro, therapeutic genes introduced and the genetically reconstituted cells autologously transplanted back into the patients. Research has progressed from pre- clinical animal models to clinical trials to treat patients with severe combined immunodeficiency syndrome and familial hypercholesterolemia, and there are currently over 60 NIH approved clinical trials. While the initial results are encouraging, the procedure is complicated and recent development has focused on the "in vivo paradigm", in which genes are directly introduced into target organs. Technology development for in vivo gene delivery has progressed at a remarkable rate during the past few years. Recombinant viral vectors started with the retrovirus, and other systems based on the adenovirus, adeno-associated virus and herpes simplex virus are rapidly becoming legitimate alternative vectors for gene delivery into various organs. Furthermore, non-viral DNA-based vectors and their delivery systems are being developed as gene medicines which include cationic lipids, receptor-mediated endocytosis, endosomal release, and nuclear translocation elements. The disease indications have also broadened from genetic disorders such as severe combined immunodeficiency syndrome, familial hypercholesterolemia, hemophilia and cystic fibrosis to acquired diseases such as cancer, various neurological disorders and infectious diseases such as AIDS. Bringing together leading investigators in each of these disciplines to engage in a vigorous scientific dialogue will expedite further basic science and clinical developments in order to achieve the goal of advancing gene therapy technology from the benchside to the bedside.